DESCRIPTION: This renewal application seeks to investigate how vitamin A regulates mucous cell differentiation in airway epithelium. Two stages of mucous cell differentiation are proposed. In the first stage, cells are unable to differentiate into mucous cells in response to vitamin A. However, they can be transformed into mucin-producing cells by microinjection of RNA from differentiated mucous cells. This first stage is therefore termed the "competent" stage of mucous cell differentiation, and vitamin A can cause immortalized airway epithelial cell lines to become competent. In the second "progressive" stage, vitamin A induces mucous cell differentiation. Dr. Wu has identified one to three genes from progressive stage cells which cause stage 1 cells to express mucins. This proposal seeks to clone and to characterize these genes, to define the level of regulation by vitamin A (i.e., transcription or translation), to elucidate the expression of these genes in airway epithelium, and finally to define the mechanism by which these genes induce mucous cell differentiation.